Modern Research on Ginger

Ginger (Zingiber officinale) is a member of a plant family that includes cardamom and turmeric. For thousands of years ginger has been used as both a spice and an herbal medicine. It was a highly sought commodity exported from India to the Roman Empire, and then controlled by Arab merchants for centuries. The popular “Gingerbread Man” cookie shape is said to be the inspiration of Queen Elizabeth I of England.

The part of the ginger plant that is used in both cooking and herbal medicine is the root or rhizome—the horizontal stem from which the roots grow. The primary producer of ginger is still India, although it is also cultivated in East Africa, the Caribbean, and throughout the tropics.

In Ayurveda, ginger root is referred to as either Shunthi Nagara (dry), or Ardaka (fresh). It pacifies both Kapha and Vata, but if taken in excess, can aggravate Pitta. Its taste or rasa is pungent when fresh, and sweet when dry. It energetic action is heating and it is useful in stimulating agni, the digestive power. Traditional use includes the promotion of a healthy appetite and digestion, calming upset stomachs, reducing gas, helping with menstrual cramps, nausea, colic, vomiting, indigestion, colds, cough, joint pain and arthritis, asthma, congestive conditions, and as an aphrodisiac.

PubMed lists over 1700 research papers on ginger, revealing important properties which include antimicrobial, antioxidant, anti-inflammatory, antiemetic, antidiabetic, and anticancer. For example, ginger has recently been shown to have a range of antimicrobial effects (1-3), and in certain cases fresh ginger is found to be more effective than the dry ginger (4). A large number of studies have been conducted on the antioxidant properties of ginger. The bioactive molecules of ginger include the gingerols, and when dried or cooked, gingerol analogues such as zingerone and shogaol. Studies have shown that 6-shogaol exhibits the most potent antioxidant and anti-inflammatory properties, followed by 10-gingerol (5). Of all the spices, ginger is one of the strongest antioxidants (6,7).

The antioxidant properties of ginger and it principle components are thought to be responsible for its many protective effects on different organ system in the body (8-15). For example, 6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice(16). Several studies have shown that ginger suppresses lipid peroxidation and protects the levels of reduced glutathione (17,18). Further studies show that ginger prevents degeneration of the kidney cells and reduces the severity of kidney damage caused by certain antibiotics (19). In a study in Egypt published in 2008 researcher found a valuable effect of ginger extract against acetic acid-induced ulcerative colitis possibly by its antioxidant and anti-inflammatory properties (20). Other studies suggests that ginger can reduce cell death and restore motor function in animal spinal cord injury and can have a neuroprotective function from chemical induced neurotoxicity (21, 22). Further studies have demonstrated the effects of ginger and its components on protection from radiation (23-25).

A number of studies have documented the anti-inflammatory effects of ginger and its components (26-33). Ginger has been studied as a possible therapeutic agent for osteoarthritis. In one of the first studies conducted in India and published in 1992, relief from both pain and swelling was reported in patients suffering from rheumatoid arthritis, osteoarthritis, and general muscular discomfort, when using powdered ginger as a dietary supplement from 3 months to 2 years (34). One of the few studies in which positive results were not found was conducted in Copenhagen, Demark, and published in 2000, in which ginger extract was compared to placebo and Ibuprofen in patients with osteoarthritis of the hip or knee in a controlled, double blind, cross-over study. No significant difference between the placebo and the ginger extract were demonstrated although explorative tests of differences in the first treatment period showed a better effect of both Ibuprofen and ginger extract than placebo (35).

In a study conducted in Florida and published in 2001, patients with osteoarthritis of the knee with moderate-to-severe pain were enrolled in a randomized, double-blind, placebo-controlled, 6-week study. Among 247 evaluable patients, the percentage of responders experiencing a reduction in knee pain on standing was superior in the ginger extract group compared with the control group (36). In a recent randomized controlled trial conducted in Thailand, patients with osteoarthritis of the knee were given either plygersic gel, which contains a combination of ginger (Zingiber officinale) and plai (Zingiber cassumunar), or diclofenac gel. Both groups had significantly improvement in knee joint pain, symptoms, daily activities, sports activities, and quality of life, as measured by the Knee Injury and Osteoarthritis Outcome Score. There were no differences in the results between the Plygersic and diclofenac gel groups (37).

Several studies were conducted at Georgia College and State University on muscle pain. In the first study, consumption of 2 g of ginger before 30 minutes of cycling exercise had no effect on quadriceps muscle pain, the rate of perceived exertion, work rate, heart rate, or oxygen uptake These results were consistent with related findings showing that ingesting a large dose of aspirin does not acutely alter quadriceps muscle pain during cycling, and this suggests that prostaglandins do not play a large role in this type of exercise-induced skeletal-muscle pain (38). In a second study published in 2010, the researchers conducted a double-blind, placebo controlled, randomized experiments with 34 and 40 volunteers using of 2 g of ginger, either raw or heated, for 11 days. The results showed moderate-to-large reductions in muscle pain in exercise-induced muscle injury (39). Results of a double-blind comparative clinical trial indicated that ginger (250-mg capsules) was as effective as the nonsteroidal anti-inflammatory drugs in relieving pain in women with primary dysmenorrhea (40).

Anti-nausea Effects of Ginger

Throughout history ginger has been used to relieve nausea and vomiting. The antiemetic properties of ginger have been studied extensively, especially in connection with both pregnancy and chemotherapy-induced nausea and vomiting (41-44). In a study published in the medical journal Lancet in 1982, ginger was reported to be superior to both dimenhydrinate (Dramamine) and to a placebo against motion sickness, using a rotating chair to evoke the symptoms (45). A follow-up study conducted in Demark on naval cadets in the open sea, indicated that 1g of ginger every four hours reduced the tendency to vomiting and cold sweating significantly better than a placebo. There was also a marked reduction in nausea and vertigo but it was not statistically significant (46). A study published in 2002 and conducted in Taiwan, found that ginger was effective in the prevention and treatment of motion sickness as indicated by a reduction in nausea, tachygastric activity, and vasopressin release (47). In a study at the Louisiana State University Medical Center, Shreveport, the researchers found that powdered ginger provided no protection against motion sickness using a system of measurement which was based on a combination of five cardinal symptoms including nausea, pallor, cold sweats, increased salivation, and drowsiness (48). It has been suggested that the discrepancy between the results of this study and the others may be due to the fact that other studies relied primarily on the correlation between motion sickness and nausea and vomiting, rather than the other symptoms. A variety of mechanisms have been postulated for the actions of ginger and its components on nausea, some of them based on the fact that ginger has been demonstrated to affect serotonin receptors (49-51).

Another important area that has been studied extensively is the effect of ginger on nausea and vomiting during pregnancy (52-57). A research study conducted in Thailand, and reported in 2001, looked at 70 pregnant women with morning sickness. They found that after using just 1 gram of dry ginger per day for only four days, 87.5% of the ginger-takers had significant improvement in nausea symptoms compared to the placebo group (58). In another study in Iran and published in 2008, woman who received ginger (250-mg capsules) appeared to experience less vomiting and nausea compared to those receiving placebo; the ginger group also had relief from primary dysmenorrhea symptoms (59). A further study also conducted in Iran showed that ginger was more effective than vitamin B6 for relieving the severity of nausea, and was equally effective for decreasing the number of vomiting episodes in early pregnancy (60). In the latest review articles, the authors suggest that the best available evidence suggests that ginger is a safe and effective treatment for nausea and vomiting during pregnancy. They point out, however, that there are still questions regarding the maximum safe dosage of ginger, appropriate duration of treatment, consequences of over-dosage, and potential drug-herb interactions (61, 62).

Research results on the effects of ginger on chemotherapy induced nausea and vomiting has been mixed (63,64). A few studies found conflicting results, indicating that ginger had no effect on chemotherapy induced vomiting (65, 66). Most other studies have reported that there was a decrease in chemotherapy induced vomiting with the use of ginger powder (67,68). A randomized double-blind and placebo-controlled clinical trial was conducted on 80 women in Iran with breast cancer undergoing chemotherapy, and included anticipatory as well as delayed chemotherapy induced vomiting. The ginger group fared significantly better during the anticipatory acute and delayed phases (69). In a second randomized clinical trial in Iran of 100 women with advanced breast cancer, ginger was added to a standard antiemetic therapy and it reduced the prevalence of nausea 6 to 24 hours postchemotherapy (70). Finally, a study in Rochester Medical Center, New York, of 576 patients in a randomly assigned clinical trial showed that ginger supplementation at a daily dose of 0.5 g-1.0 g significantly aids in reduction of the severity of acute chemotherapy-induced nausea in adult cancer patients (71).

Two other areas of interest are the effects of ginger on postoperative vomiting and on preventing nausea associated with gynecological laparoscopy. The results are mostly positive (72-77) but there are some contradictory findings (79,80). As a whole, the majority of studies suggest that ginger is effective in alleviating nausea and vomiting associated with a number of different conditions. It was suggested at one time by European authorities that ginger should be avoided during pregnancy on theoretical grounds, but this has been disputed by others based on the fact that ginger has been used for many thousands of years by pregnant woman with no reported problems.

Diabetic and Cardiovascular Effects of Ginger

In one recent review, the researcher concluded that ginger shows effective glycaemic control properties in diabetes mellitus (81). There are mixed findings on the ability of ginger to lower lipid levels, although it appears to have other beneficial effects for cardiovascular disease. In an early study in Israel on the development of atherosclerosis in apolipoprotein E-deficient mice, ginger was shown to significantly lowered blood glucose, serum total cholesterol, LDL, VLDL, and triglycerides, and raised HDL (82). Several studies conducted in India on rabbits showed that ginger acted as an antihyperlipidaemic agent and, although it did not lower blood lipids, it significantly lowered (50%) the development of atheroma in the aorta and coronary arteries of rabbits that were fed cholesterol, as well as decreasing lipid peroxidation and enhancement of fibrinolytic activity (83, 84). Further studies showed the protective effects of ginger on the development of metabolic syndrome in an animal model (85). Several studies have shown its ability to affect insulin secretion, and to increase insulin sensitivity (86-89). This, combined with other data which shows the anti-inflammatory, antioxidant, anti-platelet, hypotensive, and hypolipidemic effects, suggests that ginger could be used in the treatment of diabetes and cardiovascular disease (90).

Attempts have also been made to determine the possible mechanism of how ginger and its components may prevent atherosclerosis or other lipid-binding diseases. One study found that ginger could have a synergetic effect on antiplatelet aggregation medication in normal human volunteers and hypertensive patients (91). A recent study investigated the activity of (S)-

[6]-gingerol to inhibit transforming growth factor. This factor stimulates proteoglycan synthesis, leading to increased binding of low-density lipoproteins, which is the initiating step in atherosclerosis (92). There have also been investigations into the anti-clotting effects of ginger and its possible interaction with warfarin (93-95). At least one study indicates that ginger at recommended doses does not significantly affect clotting status or the pharmacokinetics or pharmacodynamics of warfarin in healthy subjects (95). Another study on human subjects conducted in Iran and published in 2008, conducted a double blind controlled clinical trial in which patients with hyperlipidemia were randomly divided the into 2 groups, a treatment group (receiving ginger capsules 3 g/day in 3 divided doses) and a placebo group (lactose capsule 3 g/day in 3 divided doses) for 45 days. Triglyceride, cholesterol, and LDL levels were substantially decreased in the ginger group compared to placebo group. The high-density lipoprotein (HDL) and level of high density lipoprotein level in the ginger group increased significantly as compared to the placebo (96).

The Effects of Ginger on Asthma and Migraine

In a study done in France the researchers found that [6]-gingerol, a major constituent of ginger, was sufficient to suppress eosinophilia. This suggested that ginger could suppress Th2-mediated immune responses and might thus provide a possible therapeutic application in allergic asthma (97). A study in Canada shown that ginger inhibits airway contraction and associated Ca (2+) signalling, possibly via blockade of plasma membrane Ca(2+) channels, thus reiterating its effectiveness in treating respiratory illnesses (98). A further study on isolated human airway smooth muscles, showed that ginger and its isolated active components, [6]-gingerol, [8]-gingerol, and [6]-shogaol, caused significant and rapid relaxation, and [8]-gingerol attenuated airway hyper-responsiveness, in part by altering [Ca(2+)](i) regulation, suggesting that ginger may have a therapeutic application in airway diseases such as asthma (99).

Several studies have investigated the effects of ginger and other herbs on migraines. In a study done in the US and published in 2005, researchers 29 subject completed a one year study which looked at the effects of a compound known as GelStat Migraine, which consisted of a combination of ginger and feverfew. Two hours after treatment, 48% were pain-free with 34% reporting a headache of only mild severity. 29% reported a recurrence within 24 hours. Side effects were minimal and not serious. The authors concluded that GelStat Migraine was as effective as a first line treatment for migraine when initiated early during the milder headache phase (100). In a second study by the same research group. a double blind placebo controlled study was conducted on 60 patients using a sublingual combination of feverfew and ginger called LIpiGesic M. Again, positive results were found and it was concluded that this treatment was safe and effective as a first-line abortive treatment for a population of migraineurs who frequently experience mild headache prior to the onset of moderate to severe headache (101). In a study conducted in Iran and published in 2013, a comparison was made between the efficacy of ginger and the drug, Sumatriptan, in a double-blinded randomized clinical trial of 100 patients who had acute migraine without aura. Two hours after using either drug, mean headaches severity decreased significantly. The efficacy of ginger powder and sumatriptan was similar, while the clinical adverse effects of ginger powder were less than sumatriptan (102).

Anti-cancer effects and mechanisms of action

The anticancer potential of ginger and its active components is well documented and continues to be an active area of research (103-105). Studies in animal models have shown that ginger and its components inhibit cancer in the stomach and gastrointestinal tract (106,107), colon and lung (108-113), skin (114-119), breast (120, 121), prostate (122-124), leukemia (125), and ovarian (126). The active ingredients of ginger (e.g. [6]-gingerol,[6]-shogaol, [6]-paradol, and zerumbone) exhibits numerous types of antitumorigenic activities and as a result there are many different theories on the mechanism of how ginger might affects cancer, such as: up-regulation of carcinogen detoxifying enzymes, pro-apoptotic activity, and as an inhibitor of metastasis or angiogenesis through the modulation of NF-kappaB pathways (103-138).

A careful analysis made in one study on the effective dose of ginger for anticancer purposes suggests that it is important to consider ginger as a whole food since the beneficial effects of ginger may be due to additive or synergistic effects of other constituent phytochemicals within it (123). The authors cite another researcher who also suggests that the cancer preventive effects of plants are based on the synergistic effects of the compounds within them (139,140). This concept may explain why single phytochemicals have met with limited success, suggesting that they may lose their bioactivity without the other compounds present. In principle, lower dose levels could be used when taken as a whole food, as opposed to taking larger doses of active ingredients where the effects in humans are not well understood.